Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat

Abstract

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased alpha2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to "program" behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

Figure 1

Mean ± SEM frequency of maternal contact (the total of all behavioral categories involving contact between mother and pups), arched-back nursing, and licking/grooming in high versus low LG-ABN mothers over the first 10 days postnatally. The data represent the frequency of the behavior from a total of 1,200 observations per mother (120 observations per mother per day). ∗, P < 0.01. (Lower Right) Mean ± SEM frequency of licking/grooming over 2-day blocks for high versus low LG-ABN mothers. These data are derived from 240 observations per mother for each block. Differences between the groups were significant (P < 0.05) for days 1–8, but not on days 9–10.

Figure 2

(Top) Mean ± SEM time spent in exploration of the inner area of an open field in the adult offspring of high versus low LG-ABN mothers. ∗∗∗, P < 0.001. The scattergrams depict the correlation between maternal licking/grooming (Middle) and arched-back nursing (Bottom) and exploration.

Figure 3

Mean ± SEM latency to begin eating (Upper) and time eating (Lower) in a novel environment for the adult offspring of high (n = 10) versus low (n = 6) LG-ABN mothers. ∗, P < 0.01.

Figure 4

(Top) Mean ± SEM central benzodiazepine receptor ([³H]flunitrazepam) binding (in fmol/mg of protein) in the adult offspring of high versus low LG-ABN mothers. ∗, P < 0.01. The scattergrams depict the correlation between maternal licking/grooming (middle) and arched-back nursing (Bottom) and [³H]flunitrazepam binding in the central nucleus of the amygdala.

Figure 5

(a) Mean ± SEM α₂ adrenoreceptor ([³H]clonidine) binding (in fmol/mg of protein) in the adult offspring of high versus low LG-ABN mothers. ∗, P < 0.05. (b) Mean ± SEM ¹²⁵I-CRH binding (in fmol/mg of protein) in the adult offspring of high versus low LG-ABN mothers. ∗∗, P < 0.01.